title: The importance of being short: the role of rabies virus phosphoprotein isoforms assessed by differential IRES translation initiation.
abstract: The rabies virus (RV) phosphoprotein P is a multifunctional protein involved in viral RNA synthesis and in counteracting host innate immune responses. We have previously shown that RV P gene expression levels can be regulated by using picornavirus internal ribosome entry site (IRES) elements. Here we exploited a particular feature of the foot-and-mouth disease virus (FMDV) IRES, namely, preferential initiation at a downstream initiation codon, to address the role of N-terminally truncated RV phosphoproteins usually generated in RV-infected cells through ribosomal leaky scanning. Recombinant RVs in which P synthesis was directed by the poliovirus or FMDV IRES produced full-length P (P1) or a truncated form (P2), as the dominant product, respectively. While the P2 overexpressing virus showed attenuated growth in interferon-incompetent cells, it was superior to the P1 overexpressing virus in preventing expression of host interferon-stimulated genes. This indicates that in RV infected cells the availability of the truncated P2 protein is critical for viral resistance to interferon.
authors.affiliation: Max von Pettenkofer-Institute & Gene Center, Ludwig-Maximilians-University Munich, Feodor-Lynen-Strasse 25, Munich, Germany.
authors.forename: Adriane
authors.initials: A
authors.lastname: Marschalek
authors.forename: Lisa
authors.initials: L
authors.lastname: Drechsel
authors.forename: Karl-Klaus
authors.initials: KK
authors.lastname: Conzelmann
mesh_terms: D000818:Animals; D002460:Cell Line; D018387:Codon, Initiator / Q000235:genetics; D006224:Cricetinae; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D029544:Foot-and-Mouth Disease Virus / Q000737:chemistry / Q000235:genetics; D017930:Genes, Reporter; D005818:Genetic Engineering / Q000379:methods*; D016679:Genome, Viral; D007372:Interferons / Q000096:biosynthesis* / Q000276:immunology; D008156:Luciferases / Q000032:analysis; D018832:Molecular Chaperones; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010957:Plasmids; D017955:Poliovirus / Q000737:chemistry / Q000235:genetics; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011818:Rabies / Q000276:immunology / Q000821:virology*; D011820:Rabies virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D018387:Codon, Initiator; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D020033:Protein Isoforms; D014764:Viral Proteins; D015678:Viral Structural Proteins; D007372:Interferons; D008156:Luciferases; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases